The Importance of Clinical Trials

The Importance of Clinical Trials & Research: Hope For The Future

Chief, Laboratory of Clinical Infectious Diseases National Institute for Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland

This overview explains the importance of clinical trials and research in the study of nontuberculous mycobacterial (NTM) infections.

Until recently, the study of NTM was largely derived from what we learned about tuberculosis (TB) over the years. This TB information has proven extremely valuable but has also been somewhat limiting. Once an infection is determined to be nontuberculous, many medical professionals lose interest in what to do about it. This is changing and although it may have been appropriate from a public health standpoint 50 years ago, it certainly is no longer the case today. Many physicians now report seeing more cases of NTM than TB. Therefore, the study of NTM infections needs to be established on its own foundation and basis so that we can ensure appropriate understanding and treatment.

What are the key questions in basic research for NTM?

Key questions in NTM research include the areas of epidemiology, environment, growth and survival, virulence, and unique drug targets. These elements are the critical ones that need to be understood if we are to have insight into who gets infected, how infection occurs, the role of those infections in disease, the ability to identify those infections over time, and the ability to treat those infections. Without adequate basic research, we will spend the next 50 years wondering why thinking of NTM as a cousin to TB is not as effective as it could be. Just as treating one NTM patient identically to his or her sister is liable to be unsuccessful, treating NTM infection as if it is simply a close relative to TB will have the same pitfalls.

What is applied (or translational) research and what does it mean in relation to NTM infection?

Applied research is performed to answer specific, practical questions. It uses basic scientific information to find ways to improve our approaches to problems. In relation to NTM, applied research aims at resolving or reducing the effects of NTM related health problems through treatments, therapies, medications, etc. The goal is to use basic observations to understand clinical disease. If we lump these two together, we are looking at observations about epidemiology, virulence, susceptibility, etc. and how to use these observations in a human context. An example would be an attempt to identify drug targets, and then testing those targets with drugs (already available or in development) that might not otherwise be used for NTM infection. In addition, we could conduct research that looks at epidemiological aspects of NTM, and then identify issues of susceptibility (age of onset, gender, specificity, family clustering). Translational research might come into play here, for instance, in studying patients with specific illnesses to understand the genes that cause those illnesses.

What are clinical trials and why are they important?

Clinical trials are the foundation on which modern medical recommendations should be based. It is extremely difficult to be certain what works, especially when you desperately want something to work. As we know from our own experiences with the world around us, not everything that we desire to be true turns out to be so. The only way to accurately and reliably identify, understand and verify medical truth is through a clinical trial. In a clinical trial, one potential therapy is tried out against another. Usually, one therapy is the standard of care, and one is experimental. This type of clinical trial is particularly difficult in a disease like NTM infection, since even the standard of care has never been rigorously demonstrated to be effective. There are different approaches to patients at different treatment centers and even at different times. It is not likely that all treatments are all equally effective, but we are genuinely stymied in determining which approach is the most effective.

The way to achieve a truly informative clinical trial, where we learn more about treatments that really work well, is to conduct a clinical trial that compares one approach to another. This will give us the opportunity to look at real numbers and data, giving us real answers about how to treat real patients. The most persuasive clinical trials are those that involve multiple centers and patients, and are randomized (that is, in which the decision about enrollment in a given treatment is left to chance). These trials help prevent the influence or potential bias in investigators and even patients that could affect the outcome by providing skewed information. Unfortunately, there have not been many prospective trials for NTM infection. Efforts to get such trials started are in planning, but they tend to be large, expensive, complicated and slow to get started. It is hoped that patients will recognize the critical need for participation. While participation in a specific trial will not necessarily make any one patient’s life better it will help the medical field move forward to identify new therapies.

We hope the preceding has helped to identify why research and trials are so important in understanding and treating nontuberculous mycobacterial infections. The way that clinical trials are done is absolutely and critically dependent on a partnership between patients, physicians, and investigators.

Without this partnership being robust, interactive, and equal, things will not get better. TOGETHER, PHYSICANS, PATIENTS AND GOVERNMENT CAN PROVIDE LEADERSHIP, HOPE AND ANSWERS.